A Zinc Oxide Nanowire-Modified Mineralized Collagen Scaffold Promotes Infectious Bone Regeneration.

Bone infection poses a major clinical challenge that can hinder patient recovery and exacerbate postoperative complications. This study has developed a bioactive composite scaffold through the co-assembly and intrafibrillar mineralization of collagen fibrils and zinc oxide (ZnO) nanowires (IMC/ZnO). The IMC/ZnO exhibits bone-like hierarchical structures and enhances capabilities for osteogenesis, antibacterial activity, and bacteria-infected bone healing. During co-cultivation with human bone marrow mesenchymal stem cells (BMMSCs), the IMC/ZnO improves BMMSC adhesion, proliferation, and osteogenic differentiation even under inflammatory conditions. Moreover, it suppresses the activity of Gram-negative Porphyromonas gingivalis and Gram-positive Streptococcus mutans by releasing zinc ions within the acidic infectious microenvironment. In vivo, the IMC/ZnO enables near-complete healing of infected bone defects within the intricate oral bacterial milieu, which is attributed to IMC/ZnO orchestrating M2 macrophage polarization, and fostering an osteogenic and anti-inflammatory microenvironment. Overall, these findings demonstrate the promise of the bioactive scaffold IMC/ZnO for treating bacteria-infected bone defects.

Mussel-Inspired Multicomponent Codeposition Strategy toward Antibacterial and Lubricating Multifunctional Coatings on Bioimplants.

Bacterial infections and limited surface lubrication are the two key challenges for bioimplants in dynamic contact with tissues. However, the simultaneous lubricating and antibacterial properties of the bioimplants have rarely been investigated. In this work, we successfully developed a multifunctional coating with simultaneous antibacterial and lubricating properties for surface functionalization of bioimplant materials. The multifunctional coating was fabricated on a polyurethane (PU) substrate via polydopamine (PDA)-assisted multicomponent codeposition, containing polyethyleneimine (PEI) and trace amounts of copper (Cu) as synergistic antibacterial components and zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) as the lubricating component. The obtained PDA(Cu)/PEI/PMPC coating showed excellent antibacterial activity (antibacterial efficiency: ∼99%) to both Escherichia coli and Staphylococcus aureus compared with bare PU. The excellent antibacterial properties were attributed to the combined effect of anti-adhesion capability of hydrophilic PMPC and PEI and bactericidal activity of Cu in the coating. Meanwhile, the coefficient of friction of the coating was significantly decreased by ∼52% compared with bare PU owing to the high hydration feature of PMPC, suggesting the superior lubricating property. Furthermore, the PDA(Cu)/PEI/PMPC coating was highly biocompatible toward human umbilical vein endothelial cells demonstrated by in vitro cytotoxicity tests. This study not only contributes to the chemistry of PDA-assisted multicomponent codeposition but also provides a facile and practical way for rational design of multifunctional coatings for medical devices.

Controlling the two components modified on nanoparticles to construct nanomaterials.

Nanoparticle self-assembly technology has made great progress in the past 30 years. Many kinds of self-assembly strategies of modifiable nanoparticles have been developed and used to construct nano-aggregates by designing the shape, size and type of nanoparticles and controlling the components modified on nanoparticles. These strategies are widely used in many fields, such as medical diagnosis, biological detection, drug delivery, materials synthesis and sensors. The modified components can be DNA chains, polymer chains, proteins, and even organic molecules based on different molecular conformations and chemical properties. In recent years, the self-assembly of two-component modified nanoparticles has gradually attracted more attention. Nanoparticles modified with two components of different DNA strands can self-assemble to produce a variety of nano arrangement structures, such as BCC, FCC and other cubic crystals, which can be used in crystal materials. Two-component modification of hydrophilic and hydrophobic polymers can produce vesicular aggregates, which can be used for drug delivery. In this review, we summarize the latest experimental progress and theoretical simulation of self-assembly of two-component modified nanoparticles including different DNA chains, different polymer chains, DNA and polymer chains, proteins and polymer chains, and different organic molecules. Their self-assembly characteristics and application prospects were discussed. Compared with single-component modified nanoparticles, two-component nanoparticles have different tethered molecules or molecular chains, which can be multifunctional by regulating different modified components and types of nanoparticles and ultimately expand the scope of applications.

An Innovative and Economical Device for Ischemic Preconditioning of the Forehead Flap Prior to Pedicle Division: A Comparative Study.

BACKGROUND: Ischemic preconditioning of the forehead flap prior to pedicle division helps to improve angiogenesis. Clamping the pedicle by a clamped rubber band with vessel forceps is often clinically applied. However, the severe pain and unstable blocking effect influenced the preconditioning process. In this study, we described an innovative device designed for ischemic preconditioning and compared its efficacy with the clamped rubber band. METHODS: The device consists of a self-locking nylon cable tie with a buckle and a rubber tube. The rubber tube is fed over the cable tie to act as a soft outer lining and the cable tie is tightened across the pedicle to block the perfusion for ischemic preconditioning. This device and the standard clamped rubber band were applied respectively before division surgery. The constriction effect, reliability, reproducibility, and the patients' pain tolerance were compared. RESULTS: A total of 20 forehead flaps were included. The cable tie had less incidence of loosening (7.7% vs. 16.6%, p < 0.05) and maintained the pressure more effectively. The pain score for the nylon cable tie was significantly lower than the clamped rubber band (4.25 ± 1.02 vs. 6.75 ± 1.12, p < 0.05), especially for 10 pediatric patients (4.50 ± 0.85 vs. 8.10 ± 1.20, p < 0.01). All 20 pedicles were successfully divided at 19 to 22 days with no surgical complications. CONCLUSION: Compared with the clamped rubber band, the cable tie produces a more reliable and reproducible ischemic preconditioning effect. It is also better tolerated by the patients. Therefore, we recommend using the nylon cable tie as the preferred device for ischemic preconditioning of the forehead flap.

Processing of fast-gelling hydrogel precursors in microfluidics by electrocoalescence of reactive species.

Microscopic hydrogels, also referred to as microgels, find broad application in life and materials science. A well-established technique for fabricating uniform microgels is droplet microfluidics. Here, optimal mixing of hydrogel precursor components is crucial to yield homogeneous microgels with respect to their morphology, mechanics, and distribution of functional moieties. However, when processing premixed polymer precursors that are highly reactive, fast or even instantaneous gelation inside fluid reservoirs or the microchannels of the flow cell commonly occurs, leading to an increase of fluid viscosity over time, and thus exacerbating the intrinsic control over fluid flow rates, droplet and microgel uniformity, which are key selling points of microfluidics in material design. To address these challenges, we utilize microflow cells with integrated electrodes, which enable fast addition and mixing of hydrogel precursors on demand by means of emulsion droplet coalescence. Here, two populations of surfactant-stabilized aqueous droplets - the first containing the material basis of the microgel, and the second containing another gel-forming component (e.g., a crosslinker) are formed at two consecutive microchannel junctions and merged via temporary thin-film instability. Our approach provides the ability to process such hydrogel systems that are otherwise challenging to process into uniform droplets and microgels by conventional droplet microfluidics. To demonstrate its versatility, we fabricate microgels with uniform shape and composition using fast hydrogelation via thiol-Michael addition reaction or non-covalent self-assembly. Furthermore, we elucidate the limitations of electrocoalescence of reactive hydrogel precursors by processing sodium alginate, crosslinked by calcium-induced ionic interactions. For this instantaneous type of hydrogelation, electrocoalescence of alginate and calcium ions does not result in the formation of morphologically isotropic microgels. Instead, it enables the creation of anisotropic microgel morphologies with tunable shape, which have previously only been achieved by selective crosslinking of elaborate higher-order emulsions or by aqueous two-phase systems as microgel templates.

Comparative Microbial Profiles of Caries and Black Extrinsic Tooth Stain in Primary Dentition.

Extrinsic black tooth stain (BS) is a common oral disease associated with lower caries experience in preschool children, although the microbiotic features contributing to the low risk of caries in this group remain elusive. In this study, we aimed at identifying the dominant bacteria in dental plaque to indicate the incidence of caries in the primary dentition. Subjects were divided into 3 groups based on the clinical examination: group CF, children without pigment who had no caries lesions or restorations (n = 18); group CS, children who were diagnosed with severe early childhood caries (n = 17); and group BS, children with pigment (black extrinsic stain) without caries or restorations (n = 15). The total microbial genomic DNA was extracted and subjected to bacterial 16S ribosomal RNA gene sequencing using an Illumina HiSeq platform. The differential dominant bacteria were determined using Wilcoxon rank-sum testing and linear discriminant analysis effect size (LEfSe). Co-occurrence network analysis was performed using sparse correlations for compositional data, calculation and functional features were predicted using PICRUSt. Interestingly, our results showed that the relative abundance of Pseudopropionibacterium, Actinomyces, Rothia, and Cardiobacterium was from high to low and that of Porphyromonas was low to high in the BS, CF, and CS groups, consistent with the clinical incidence of caries in the 3 groups. Moreover, an increased level of Selenomonas_3, Fusobacterium, and Leptotrichia was associated with high caries prevalence. We found that the interactions among genera in the BS and CS plaque communities are less complex than those in the CF communities at the taxon level. Functional features, including cofactor and vitamin metabolism, glycan biosynthesis and metabolism, and translation, significantly increased in caries plaque samples. These bacterial competition- and commensalism-induced changes in microbiota would result in a change of their symbiotic function, finally affecting the balance of oral microflora.

Septal Reconstruction With Folded Porous Polythylene Implants: An Alternative Technique for the Correction of Severe Saddle Nose Deformities in Asian Populations.

BACKGROUND: Congenital or secondary deficiency in septal cartilage leads to an unpleasant cosmetic appearance and compromised function as well. Rhinoplasty maneuvers such as spreader graft and septal extension graft with autologous tissue have been exhibited to correct the deformities. However, the relatively severe donor site morbidity stands as a main concern for both surgeons and patients. METHODS: From January of 2014 to April of 2018, 52 patients presenting septal deformities underwent rhinoplasty with our modified technique. A piece of Medpor (8438) was tailored, folded and then placed as a combination of spreader and septal extension graft. The surgical outcomes were evaluated both objectively and subjectively. RESULTS: All the patients were followed up for 12 to 24 months postoperatively. The ratio of tip projection and the nasal length exhibited significant improvement in all our patients. Nasal obstruction subjectively mended among the 24 patients who had airway obstruction complaint preoperatively. Only 2 patients had severe adverse events and the implants were removed instantly. CONCLUSIONS: With our modified technique, Medpor proved to be an effective and reliable material for the reconstruction of septal cartilage, which provides us an alternative way to achieve extended spreader and septal extension graft with one single implant in the correction of saddle nose.Level of Evidence: Level IV, therapeutic study.

Exosomes derived from maxillary BMSCs enhanced the osteogenesis in iliac BMSCs.

OBJECTIVE: Secondary alveolar bone grafting is an essential part in the treatment of alveolar cleft deformity. Autologous iliac bone is the most favorable grafting source. However, the factors regulating postoperative bone formation are unclear. Investigations are needed to found whether the alveolar bone niche and bone marrow mesenchymal stem cells (BMSCs) derived from the jaw bone (BMSCs-J) affected the osteogenesis of BMSCs from the ilium (BMSCs-I). MATERIALS AND METHODS: The effect of BMSCs-J on BMSCs-I was investigated using a co-culture model. The exosomes were purified by sequential centrifugation. The osteoblastic differentiation of BMSCs was analyzed in vitro and in vivo. RESULTS: Co-culture with BMSCs-J increased the alkaline phosphatase (ALP) activity, Alizarin Red S (ARS) staining, and osteogenic gene expression in BMSCs-I. Transmission electron microscopy and nanoparticle tracking analysis verified the presence of exosomes in the culture supernatants of BMSCs. Exosomes secreted by BMSCs-J enhanced the ALP activity, ARS staining, osteogenic gene expression of BMSCs-I in vitro, and new bone formation in vivo. Blocking the secretion of exosomes using siRNA for Rab27a inhibited the effect of BMSCs-J. CONCLUSION: Exosomes played a role in the interaction between BMSCs-J and BMSCs-I, thereby leading to the enhanced osteogenic capacity of BMSCs-I and bone formation.

Modularized Field-Effect Transistor Biosensors.

Field-effect transistors (FETs), when functionalized with proper biorecognition elements (such as antibodies or enzymes), represent a unique platform for real-time, specific, label-free transduction of biochemical signals. However, direct immobilization of biorecognition molecules on FETs imposes limitations on reprogrammability, sensor regeneration, and robust device handling. Here we demonstrate a modularized design of FET biosensors with separate biorecognition and transducer modules, which are capable of reversible assembly and disassembly. In particular, hydrogel "stamps" immobilizing bioreceptors have been chosen to build biorecognition modules to reliably interface with FET transducers structurally and functionally. Successful detection of penicillin down to 0.25 mM has been achieved with a penicillinase-encoded hydrogel module, demonstrating effective signal transduction across the hybrid interface. Moreover, sequential integration of urease- and penicillinase-encoded modules on the same FET device allows us to reprogram the sensing modality without cross-contamination. In addition to independent bioreceptor encoding, the modular design also fosters sophisticated control of sensing kinetics by modulating the physiochemical microenvironment in the biorecognition modules. Specifically, the distinction in hydrogel porosity between polyethylene glycol and gelatin enables controlled access and detection of larger molecules, such as poly-l-lysine (MW 150-300 kDa), only through the gelatin module. Biorecognition modules with standardized interface designs have also been exploited to comply with additive mass fabrication by 3D printing, demonstrating potential for low cost, ease of storage, multiplexing, and great customizability for personalized biosensor production. This generic concept presents a unique integration strategy for modularized bioelectronics and could broadly impact hybrid device development.

Robustness Testing of Mesenchymal Stem Cell Monotherapy Following Vascularized Composite Allotransplantation.

BACKGROUND: Immunosuppression risks are a major concern with vascularized composite allotransplantation (VCA). As an emerging strategy, the antirejection role played by mesenchymal stem cells (MSCs) is receiving attention. However, the current literature reports are inconclusive regarding the robustness of the MSC monotherapy. Using a rat forelimb VCA model, this study tested the robustness of the immunomodulation efficacy of gingival-derived MSCs (GMSCs) and bone marrow-derived MSCs (BMMSCs). METHODS: Forelimbs were transplanted on pairs of major histocompatibility complex-incompatible rats (Wistar-Kyoto donor, Lewis [LEW] recipient). Twenty-four LEW rats were randomly divided into four groups, including control (no treatment) and three treatment groups: rapamycin (2 mg/kg/day for 28 days, postoperatively), BMMSC and GMSC, both of which received donor-derived stem cells administered intravenously on postoperative days (PODs) 0, 3, 7, and 14. Rejection was considered as 80% skin necrosis of the allograft. Microcomputed tomography (µCT) was performed to evaluate healing at osteosynthesis site. On POD 14, limbs from each group underwent histological analysis and rejection grading using the Banff system. RESULTS: Both BMMSC (15.0 days) and GMSC (14.7 days) treatment failed to prolong VCA survival in comparison with the control group (13.8 days; p > 0.050), while the rapamycin significantly delayed acute VCA rejection (24.5 days; p = 0.003). Micro-CT imaging revealed no gross visual difference across all groups. Histology revealed that the control group was most severely affected (grades III and IV) followed by MSC (grade II) and rapamycin (grade I). CONCLUSION: MSC monotherapy, both BMMSC and GMSC, did not inhibit rejection in our VCA model. Skin immunogenicity is an important issue in promoting rejection, and a concomitant immunosuppression regimen should be considered to prolong allograft survival.

Highly Conductive, Stretchable, and Cell-Adhesive Hydrogel by Nanoclay Doping.

Electrically conductive materials that mimic physical and biological properties of tissues are urgently required for seamless brain-machine interfaces. Here, a multinetwork hydrogel combining electrical conductivity of 26 S m-1 , stretchability of 800%, and tissue-like elastic modulus of 15 kPa with mimicry of the extracellular matrix is reported. Engineering this unique set of properties is enabled by a novel in-scaffold polymerization approach. Colloidal hydrogels of the nanoclay Laponite are employed as supports for the assembly of secondary polymer networks. Laponite dramatically increases the conductivity of in-scaffold polymerized poly(ethylene-3,4-diethoxy thiophene) in the absence of other dopants, while preserving excellent stretchability. The scaffold is coated with a layer containing adhesive peptide and polysaccharide dextran sulfate supporting the attachment, proliferation, and neuronal differentiation of human induced pluripotent stem cells directly on the surface of conductive hydrogels. Due to its compatibility with simple extrusion printing, this material promises to enable tissue-mimetic neurostimulating electrodes.

Multifunctional Fe3O4@C-based nanoparticles coupling optical/MRI imaging and pH/photothermal controllable drug release as efficient anti-cancer drug delivery platforms.

Multifunctional nanomedicines featuring high drug loading capacity, controllable drug release and real-time self-monitoring are attracting increasing attention due to their potential to improve cancer therapeutic efficacy. Herein, a new kind of Fe3O4@C-based nanoparticles modified with isoreticular metal organic frameworks (IRMOF-3), folic acid (FA) and detachable polyethylene glycol (PEG) under tumor microenvironment was developed. The core-shell structured Fe3O4@C was synthesized via the one-pot solvothermal reaction and the IRMOF-3 layers were coated on the outer shell of Fe3O4@C through layer-by-layer coating method. The FA and PEG were conjugated on the surface of nanoparticles by reacting with the amine groups provided by IRMOF-3. The as-synthesized nanoparticles showed stable photothermal effect, superparamagnetic properties and blue fluorescence characteristic under 360 nm irradiation. The in vitro experiments showed that the drug loaded nanoparticles exhibit pH-dependent drug release property, and PEGylation was proved effective in suppressing burst drug release (only 8.0% of drugs were released within 95 h). The confocal laser scanning microscopy study revealed that the as-synthesized nanoparticles could serve as a cell imaging agent and the cell internalization can be significantly enhanced after FA modified. The IRMOF-3 modified nanoparticles showed negligible cytotoxicity and the drug loaded nanoparticles showed pH/photothermal-stimuli enhanced cytotoxicity in vitro. It is believed that the present smart drug delivery platforms will hold great potential in imaging guided drug delivery and cancer therapy.

Non-thermal plasma reduces periodontitis-induced alveolar bone loss in rats.

Periodontitis, a chronic infectious disease induced by microbial biofilm, is one of the most common diseases worldwide. Scaling and root planning (SRP) has always been recognized as the typical treatment. However, the therapeutic efficiency is often limited due to the intraoperative bleeding and the limitations of instruments. Non-thermal atmospheric plasma (NTP) appears to be a potential tool for periodontitis due to its promising biofilm degradation and decontamination effects. In this study, we investigated the role of NTP, as an adjuvant approach for the treatment of ligature-induced periodontitis in rats. Herein we showed that SRP or SRP-NTP application attenuated the periodontitis-induced alveolar bone loss, reflected by the increased BV/TV value and the decreased CEJ-AB distance, which might be related to the lower detection rate of periodontal pathogen in SRP and SRP-NTP groups. Besides, SRP-NTP rats showed less bone loss and lower CEJ-AB distance than that of SRP group at 30d post treatment, indicating a more comprehensive and long-lasting effect of SRP-NTP. A remarkable decrease of osteoclast number and lower expression of RANKL was also detected in SRP-NTP rats. In addition, expression of inflammatory-related cytokines such as TNF-α and IL-1ß decreased significantly in SRP-NTP group, while IL-10 level increased substantially. These results together illustrated that a combination of SRP and NTP treatment was an effective way to prevent periodontitis progress, which reduced alveolar bone loss and promoted periodontium restoration in ligature-induced periodontitis rats. In conclusion, non-thermal plasma treatment may be considered as a feasible and effective supplementary approach to control periodontitis.

Controlled and Efficient Polymerization of Conjugated Polar Alkenes by Lewis Pairs Based on Sterically Hindered Aryloxide-Substituted Alkylaluminumitle.

Reported herein is the development of an effective strategy for controlled and efficient Lewis pair polymerization of conjugated polar alkenes, including methyl methacrylate (MMA), n-butyl methacrylate (nBuMA), and γ-methyl-α-methylene-γ-butyrolactone (γMMBL), by the utilization of sterically encumbered Al(BHT)2Me (BHT: 2,6-di-tert-butyl-4-methylphenol) as a Lewis acid that shuts down intramolecular backbiting termination. In combination with a selected N-heterocyclic carbene (NHC) as a Lewis base, the polymerization of MMA exhibited activity up to 3000 h-1 TOF and an acceptable initiation efficiency of 60.6%, producing polymers with high molecular weight (Mn up to 130 kg/mol) and extremely narrow dispersity (D = 1.06~1.13). This controlled polymerization with a living characteristic has been evidenced by chain-extension experiments and chain-end analysis, and enabled the synthesis of well-defined diblock copolymers.

Dentoskeletal effects of facemask therapy in skeletal Class III cleft patients with or without bone graft.

INTRODUCTION: The association between maxillary protraction and bone graft in patients with cleft lip and palate remains unclear. The purpose of this study was to investigate whether a secondary alveolar bone graft influences dentoskeletal effects of facemask therapy in unilateral cleft lip and palate patients with a skeletal Class III relationship. METHODS: In this prospective nonrandomized clinical trial, 61 consecutive boys with unilateral cleft lip and palate and skeletal Class III malocclusion were divided into 3 groups: grafted facemask group (n = 21), ungrafted facemask group (n = 20), and untreated control group (n = 20). Sixteen dentoskeletal measurements on lateral cephalometric radiographs were compared before and after therapy or observation with 1-way analysis of variance or the Mann-Whitney U test. RESULTS: After facemask therapy, the grafted group showed a statistically significantly greater advancement of Point A (S-Vert-A, 4.18 ± 1.94 mm; SNA, 3.51° ± 2.21°) than did the ungrafted group (S-Vert-A, 2.64 ± 1.58 mm; SNA, 1.92° ± 1.05°). Furthermore, significant SNB changes were found in the grafted group when compared with those in the ungrafted group (-0.38° ± 1.77° vs -1.69° ± 1.34°; P <0.05). The changes in the mandibular plane angle (MP-SN, MP-FH) in the grafted group were less pronounced than in the ungrafted group by approximately 2° (P <0.05). Flaring of the maxillary incisors was more pronounced in treated subjects than in untreated subjects. The mandibular incisors proclined in both grafted (1.54° ± 4.21°) and control (0.97° ± 3.71°) patients, and were retroclined in the ungrafted group (-2.13° ± 3.68°). CONCLUSIONS: Facemask therapy performed after an alveolar bone graft produced more anterior maxillary migration (90%) and less pronounced mandibular clockwise rotation (10%) than those in the ungrafted group (50%, 50%, respectively).

Application of a Porous Polyethylene Spreader Graft for Nasal Lengthening in Asian Patients.

BACKGROUND: Rhinoplasty maneuvers to lengthen the nose include placing an alloplastic implant, caudally rotating the lower lateral cartilage (LLC), and stretching the soft tissue skin envelope (STSE) downward. Tissue tension associated with these procedures can result in implant extrusion or tip retraction. OBJECTIVES: The authors performed rhinoplasty with implantation of porous polyethylene (Medpor). The Medpor device enabled transfer of tension from the LLC and STSE to the juncture of the septal cartilage and upper lateral cartilage (ULC), thereby stabilizing the nasal structures. METHODS: Twenty-six patients who underwent rhinoplasty with nasal augmentation and lengthening were evaluated in a prospective study. Two pieces of Medpor were placed as a spreader graft, and a third piece was inserted as a columellar strut. The released LLC was rotated caudally, and the domal segments were wrapped over the caudally projected tip of the implant. Surgical outcomes were assessed with a patient satisfaction questionnaire and by photogrammetry. RESULTS: Patients were monitored for an average of 9.6 months. The patients' mean nasolabial angle (NLA) was 106.2° ± 4.7° preoperatively and 94.3° ± 3.7° postoperatively (t < 0.0001). Most patients were fairly or completely satisfied with the operative outcome. One patient had impending implant extrusion and underwent explanation. CONCLUSIONS: Medpor material is easy to shape and is sufficiently strong to function as a spreader graft and withstand the tension associated with repositioning of the LLC and STSE.

1α,25-Dihydroxyvitamin D3 increases implant osseointegration in diabetic mice partly through FoxO1 inactivation in osteoblasts.

Oral implant osseointegration is delayed by hyperglycemia-generated oxidative stress (OS). Forkhead transcription factor 1 (FoxO1) is known to be viewed as a sensor to OS since reactive oxide species like H2O2 regulates its activity. We previously demonstrated that 1,25(OH)2D3 favored glucose homeostasis and implant osseointegration in diabetic rats. In this study, we investigated the role of FoxO1OB in the regulation process of 1,25(OH)2D3 on glycometabolism and bone metabolism. We show herein that, with the treatment of 1,25(OH)2D3, mice lacking FoxO1 in osteoblasts (FoxO1OB-/-) exhibited decreased serum glucose that was gradually elevated in untreated diabetic mice. An optimal increase of bone mass and bone-implant contact (BIC) was observed in 1,25(OH)2D3 treated FoxO1OB-/- mice after 2-month healing. Surprisingly, FoxO1OB-/- mice without 1,25(OH)2D3 treatment also showed an improvement on bone formation and BIC. Same effect could be found in the expression of bone-related markers Runx2, Osterix and BSP, which elevated in 1,25(OH)2D3 treated FoxO1OB-/- mice as compared to untreated WT mice. In addition, in vitro study showed that high glucose induced FoxO1 nuclear localization while the effect was ameliorated by 1,25(OH)2D3 treatment. These results suggest that FoxO1OB might be involved in the regulation of 1,25(OH)2D3 on glucose homeostasis and bone formation, and that FoxO1OB might act as a key modulator of the capacity of the skeleton regulating metabolic homeostasis. Our study also provides a new idea that a combination of systemic 1,25(OH)2D3 and local FoxO1 inhibitor may be a new approach to enhance implant osseointegration.

Nasal Airway Evaluation After Le Fort I Osteotomy Combined With Septoplasty in Patients With Cleft Lip and Palate.

Septal deviation constitutes an important component of both esthetic deformity and airway compromise in patients with cleft lip and palate (CLP). The posterior parts of the nasal septum presented greater deviation than the anterior parts in patients with complete unilateral CLP. Le Fort I down-fracture provides better access to the nasal septum than intranasal incision during rhinoplasty, especially to the posterior part. This study objectively and subjectively evaluated the nasal function after Le Fort I osteotomy combined with septoplasty in patients with complete unilateral CLP. Twenty-three patients with complete unilateral CLP presenting with nasal obstruction and septum deviation were included (12-combined surgery group; 11-control group). Types of septum deviation in the patients were analyzed. Presurgical and 6-month-postsurgical acoustic rhinometry (AR) was performed for objective assessment; and the nasal obstruction symptom evaluation (NOSE) scale was used for subjective assessment. The authors used SPSS to compare the baseline and follow-up results. Acoustic rhinometry assessment showed improvements in the nasal minimal cross-sectional area (MCA), nasal resistance, and nasal volumes in 12 patients who received combined surgery. For the 2 groups, significant improvements in nasal breathing were documented (by NOSE scores) at 6 months after surgery. Simultaneous management of the maxillary dysplasia (Le Fort I osteotomy) and intranasal pathology (septoplasty) were effective for relief of nasal airway obstruction in patients with complete unilateral CLP. The combination of objective (AR) and subjective (NOSE scale) assessments allowed better evaluation of the nasal function.

Amphipathic DNA origami nanoparticles to scaffold and deform lipid membrane vesicles.

We report a synthetic biology-inspired approach for the engineering of amphipathic DNA origami structures as membrane-scaffolding tools. The structures have a flat membrane-binding interface decorated with cholesterol-derived anchors. Sticky oligonucleotide overhangs on their side facets enable lateral interactions leading to the formation of ordered arrays on the membrane. Such a tight and regular arrangement makes our DNA origami capable of deforming free-standing lipid membranes, mimicking the biological activity of coat-forming proteins, for example, from the I-/F-BAR family.

Noncovalent hydrogel beads as microcarriers for cell culture.

Hydrogel beads as microcarriers could have many applications in biotechnology. However, bead formation by noncovalent cross-linking to achieve high cell compatibility by avoiding chemical reactions remains challenging because of rapid gelation rates and/or low stability. Here we report the preparation of homogeneous, tunable, and robust hydrogel beads from peptide-polyethylene glycol conjugates and oligosaccharides under mild, cell-compatible conditions using a noncovalent crosslinking mechanism. Large proteins can be released from beads easily. Further noncovalent modification allows for bead labeling and functionalization with various compounds. High survival rates of embedded cells were achieved under standard cell culture conditions and after freezing the beads, demonstrating its suitability for encapsulating and conserving cells. Hydrogel beads as functional system have been realized by generating protein-producing microcarriers with embedded eGFP-secreting insect cells.